orexin receptor antagonists as modulators of threat sensitivity in individuals with alcohol use disorder

Conditions: Alcohol Use Disorder

Summary: the goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (aud). the main questions it aims to answer are: * does an acute dose of suvorexant (suv) and/or daily use of suv modify brain-behavior targets of aud dysfunction? * does daily suv use change alcohol behavior and if so, is this change in behavior linked to brain-behavior change? participants will be randomized to a treatment group (suv or placebo) and protocol arm, electromyography (emg) only or emg+functional magnetic resonance imaging (fmri). participants will be asked to complete the following: * baseline lab visit(s) that include the psychophysiological stress paradigm (emg only or emg+fmri, dependent upon randomization). * acute drug challenge where the participant will return to the lab to repeat the stress paradigm following administration of a single dose of either 10mg suv or placebo. * medication trial where participants will be instructed to take 10mg capsules of suv or placebo orally each night before bedtime for 4-weeks. * daily reports of medication adherence, side-effects, sleep, alcohol use, and mood will be collected via smartphones during the 4-week medication trial. * post-treatment lab visit(s) where participants will return to the lab at the end of the medication trial and complete the same stress paradigm from baseline (emg only or emg+fmri, dependent upon randomization).


Eligibility criteria:
inclusion criteria: * age 18-65. * participant is able to give informed consent. * generally medically and physically healthy as confirmed by medical history. * meet dsm-5 diagnostic criteria for current moderate or severe aud. * engage in heavy alcohol use defined as drinking equal or greater than 14 standard drinks per week if male and equal or greater than 7 standard drinks per week if female. exclusion criteria: * clinically significant medical or neurological condition (e.g., liver disease, narcolepsy, complex sleep behaviors, severe hepatic impairment, copd, severe obstructive sleep apnea). * current cognitive dysfunction (traumatic brain injury, mental retardation, organic mental syndrome, pervasive developmental disorder, or dementia). * current use of antihistamines, strong or moderate inhibitors of cyp3a liver enzymes, strong cyp3a inducers, or digoxin. * current or past dsm-5 diagnosis of mania, schizophrenia, psychosis, suicidality, major depressive disorder, or obsessive compulsive disorder. * current substance use disorder other than alcohol or mild cannabis use disorder. * treatment seeking for aud. * recent psychotropic medication use in the past 2 months. * currently smokes 5 or more cigarettes (or electronic equivalent) per day. * bmi equal or greater than 35. * engage in night-shift work. * lack of fluency in english. * presence of ferrous-containing metal in the body. * inability to tolerate small, enclosed spaces. * deafness in one or both ears. * currently pregnant (positive pregnancy test), lactating, or not agreeing to use birth control methods during the duration of the trial.

Keywords: suvorexant alcohol use disorder electromyography functional magnetic resonance imaging